The goal of this study is to search for the transduction signal in the induction of CRP in liver cells. CRP is one of the acute phase proteins that shows a dramatic increase after cellular damage or inflammation. In tissue culture, IL-6 induces maximum CRP production and secretion in human hepatoma cells at a concentration of 500 U/ml. Pretreatment of hepatoma cells with 1 nM of TPA for 24 hours increases CRP production to about 5% of the IL-6 induced level, higher doses of TPA abolished this stimulatory effect. Forskolin at 10 micro-M to 30 micro-M induced CRP production about four times greater as compared to TPA. Incubation of liver cells with both TPA and Forskolin resulted in an additive effect of both drugs. These experiments indicated that part of the IL-6 induction pathway involves protein kinase A, while the role of protein kinase C is probably minimal. Efforts to find the other pathways involved are underway.